Probiotics in a pre- and/or post surgical environment

ABSTRACT

The present invention relates generally to the field of nutrition, more particularly to the use of probiotics in nutrition. In particular the present invention relates to the use of a probiotic or of a mixture of probiotics in the manufacture of a nutritional composition or a medicament to act the colon in a pre- or post surgical environment.

The present invention relates generally to the field of nutrition, moreparticularly to the use of probiotics in nutrition and in particular tothe use of probiotics in nutrition in a pre- and/or post-surgicalenvironment.

As early as 1907, the Russian scientist, E. Metchnikoff (1845-1919),working at the Pasteur Institute in Paris, published work showing thebeneficial effects of lactic acid bacteria contained in yogurt.Metchnikoff hypothesized that a high concentration of lactobacilli inthe intestinal flora might be important for health and longevity inhumans (Metchnikoff E M, et al., The prolongation of life: optimisticstudies. London: Heinemann 1907; 161-183).

Since this time no other group of bacteria has been proposed to beresponsible for so many different beneficial effects as lactic acidbacteria, mainly lactobacilli and Bifidobacteria. These include thestimulation of macrophage phagocytosis of viable salmonella (Hatcher Get al., J. Dairy. Sci. 1993; 76:2485-2492); the enhancement of IgAproduction in intestinal secretions (Perdigon G, et al., J. Food. Proct.1990; 53:404-410), production of antimicrobial substances (Shahani K M,et al., Am. J. Clin. Nutr. 1980; 33:2448-2457; Silvia M, et al.,Antimicr. Agen. Chemother. 1987; 31:1231-1233); the inhibition of cellattachment and cell invasion by entero-virulent bacteria (Bernet M F, etal., Gut 1994; 35:483-489) and the reduction of intestinal permeabilityto macromolecules during rotavirus induced diarrhea (Isolauri E, et al.,Pediatr Res 1993; 33:548-553). Lactobacillus bacteria have also beenused with success in the treatment of relapsing Clostridium difficilecolitis (Gorbach SL, et al., Lancet 1987; 2:1519).

These beneficial properties are not shared by all Lactobacillus andBifidobacteria strains. Lactic acid bacteria that show a benefitialbiological activity are considered to be probiotics. However, not allprobiotics share the same type of benefitial biological activities. Oneexample of a Lactobacillus strain that belongs to the group ofprobiotics is the Lactobacillus johnsonii (La1)) organism (Nestlé.Lactobacillus johnsonii (La1) Scientific Overview; 1999). This strainwas isolated several years ago from the human intestinal flora at theNestlé Research Center in Lausanne.

The La1 bacteria can be considered as a probiotic because the strain is

-   -   Non-pathogenic    -   Remains viable on reaching the small intestine or the colon    -   Shows good adhesion to the intestinal mucosal membrane    -   Is a natural component of the human intestinal flora

In addition, research has demonstrated that La1 bacterial strainpossesses some other beneficial properties including:

-   -   Inhibition of the adherence of several enteropathogenic bacteria        (E Coli ssp and Salmonella spp) to human intestinal cells in        vitro    -   Anti-diarrheal effects and inhibition of invasive E Coli species    -   Effect on the prevention of H. pylori-associated diseases    -   Stimulation of immune defenses    -   Stimulation of phagocytosis    -   Stimulation of IgA production    -   Antagonism of colonization by Clostridium perfringens

The La1 bacteria strain is presently used in fermented milk specialties(Nestlé LC1 product range) which are widely marketed in Europe as a newconcept in healthy eating. No adverse events have been documented whenused by the general population, and the La1 probiotic strain can thus beconsidered as safe.

The administration of probiotic bacteria in general has beenhypothesized to affect the composition of the intestinal microflora withreduction of pathogens in favour of non-pathogens. These events mightmodulate the immune and inflammatory responses and the gut function.(Llopis, M, et al., Gut 2005 54: 955-959)

Experimental data demonstrated that the modulation of the mucosalfunction and enteric microflora by Lactobacillus plantarum reducesseptic morbidity and mortality in animals. The administration of a mixof probiotics has been shown to be more effective than antibiotics tocure pouchitis in humans (Gionchetti, Paolo et al., Gastroenterology2003, 124:1202-9.)

While the positive effects of probiotics as an aspect of modernnutrition today under normal living circumstances are widely accepted,the use of probiotics as a part of nutrition in a pre- and/or postclinical environment has never been suggested.

One reason for this might be that is commonly known that surgery shouldtake place under sterile conditions. The consumption of bacteria aspreparation for surgery and briefly after surgery appears to becontradictory to the recommended sterility.

Usually, and in stark contrast to healthy people under normal livingconditions, people in a pre- or post clinical environment usually areunder a significant amount of stress, are under heavy antibiotictreatment, might suffer from an impaired immune system and/or are at asignificant danger of being colonized by pathogenic and antibioticresistant bacteria that appear more and more often in repeatedlysterilized environments such as hospitals.

Consequently, a pre- and/or post clinical environment cannot be comparedto normal living circumstances.

Since, however, patients undergoing surgery have a high risk ofdeveloping infections, e.g., due to intraoperative contamination withenteral contents and the occurrence of bacterial translocation, it wouldbe desirable to have available a method that allows to prevent and/or toreduce of such complications and post operative sepsis.

Based on this state of the art it was the object of the presentinvention to provide the art with a method to prepare a patient as wellas possible for the special conditions in a pre- and/or post-surgicalenvironment.

This object is solved by a use in accordance with claim 1.

In particular the present inventors have unexpectedly discovered that aprobiotic or a mixture of probiotics can be used in the manufacture of anutritional composition or a medicament to act on the colon in a pre- orpost surgical environment.

A probiotic is for the purpose of the present invention amicro-organism, dead or alive or a fraction thereof, which whenadministered in adequate amounts confers a health benefit on the host.Preferably, probiotics are live micro-organisms which when administeredin adequate amounts confer a health benefit on the host.

A nutritional composition is for the purpose of the present invention anutritional balanced formulation containing adequate proportions ofmacro- and micronutrients. Those skilled in the art will understand thatthe composition of the nutritional balanced formulation will depend on anumber of factors, such as age, sex, and condition of the subject to betreated. However, those skilled in the art will be able to determine thecomposition of the formulation appropriately.

In the framework of the present invention the way by which theprobiotics act on the colon is not particularly limited. If deadprobiotics are used, these could act on the distal small bowel and theproximal colon, e.g., by releasing a significant quantity of bacteriallyassociated molecular patterns that can stimulate the immune response andpromote an homeostatic modulatory condition at the distal intestinalmucosa. Thus bacterial products or conserved molecules will interactprincipally with host cell receptors on the epithelial and dendriticcells of the mucosal compartment (S. Rakoff-Nahoum, et al., Cell. 2004118:229-241).

In contrast, living probiotics could act on the colon by passing throughit. Possible effects produced by viable probiotics passing through thecolon can be exerted by their capacity to expand and thereby to competefor available habitats in the distal intestinal environment and todisplace of pathogenic bacteria; in addition or alternatively—as theyremain metabolically active—they can prevent overgrowth of pathogens dueto metabolic products such as short chain fatty acids and the release ofbioactive molecules that can have bacteriostatic or bactericidalactivity against other bacteria. Furthermore live bacteria and themolecules released as a consequence of their metabolic activity ornatural cell death have the capacity to interact with the host immunemolecules expressed on the surface of the mucosa and thereby stimulatean immune response or induce a cytoprotective reaction of the mucosalcells.

Preferably, however, the probiotics reach the colon alive and colonizeit. This way, they establish a permanent presence and can produce a muchmore pronounced effect. In particular, the probiotics that establish alocal presence by colonization are effective in changing the ecologicalsituation of the colon by their metabolic activity.

Hence in one preferred embodiment of the present invention theprobiotics act by a reaching the colon alive, in particular bycolonizing the colon.

If probiotics colonize the colon they preferably colonize the coloniclumen and mucosal surfaces. This way they can produce the mostpronounced effect.

A consequence of the effect of probiotics on the colon is thatnon-infectious diarrhoea can be prevented and/or managed by thenutritional composition or medicament prepared by the use of the presentinvention.

A further consequence of this effect on the colon is that postsurgicalabdominal-pelvic infections due to pelvic fluid collection secondary toleakiness in the anastomosis or bacterial translocation can be preventedby the nutritional composition or medicament prepared by the use of thepresent invention.

A further consequence of this effect on the colon is thatgastrointestinal symptoms secondary to global changes in the intestinalmicrobial ecology and the microbiota metabolic activity, preferablyinfectious or toxigenic diarrhoea can be prevented and/or alleviated bythe nutritional composition or medicament prepared by the use of thepresent invention. The disturbance of normal gastrointestinal flora,particularly after antibiotic use and/or colonic surgery, is believed topredispose patients to colonization by C. difficile. The nutritionalcomposition or the medicament of the present invention containingselected probiotics that can colonize the colon, in particular thecolonic lumen and/or mucosal surfaces, can restore the equilibrium inthe altered gastrointestinal flora and thus protect against colonizationor bacterial overgrowth of potentially pathogenic bacteria.

A further consequence of this effect on the colon is thatgastrointestinal infections, preferably nosocomial gastrointestinalinfections can be prevented or treated by the nutritional composition ormedicament prepared by the use of the present invention. Suchgastrointestinal infections are often times responsible for theappearance of diarrhoea, which consequently, can be prevented and ortreated in accordance with the present invention.

Furthermore, the nutritional composition or the medicament prepared bythe use of the present invention can advantageously be used for theprevention of nosocomial colonization by methicillin-resistantStaphylococcus aureus and vancomycin-resistant enterococci or otherantibiotic resistant micro-organisms in the nosocomial environment.

In particular, according to the present invention probiotics can be usedin the manufacture of a nutritional composition and/or of a medicamentto modulate, in particular increase, the inflammatory response, inparticular during the healing process. This effect of the productsobtainable by the use of the present invention can be achieved, e.g., bystimulating the production of mucosal secretory antibodies.

The nutritional composition and/or the medicament prepare by the use ofthe present invention can be used for modulating the immune systemand/or for stimulating the production of mucosal secretory antibodies.

The kind of probiotics usable in the present invention is notparticularly limited. Any known probiotic is applicable.

However, preferably the probiotic is selected from the group consistingof Bifidobacterium, Lactobacillus, Streptococcus and Saccharomyces ormixtures thereof; more preferably the probiotic is selected from thegroup consisting of Bifidobacterium longum, Bifidobacterium lactis,Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillusjohnsonii, Lactobacillus plantarum, Lactobacillus salivarius,Streptococcus faecium, Saccharomyces boulardii and Lactobacillus reuterior mixtures thereof; and most preferred the selected probiotic isselected from the group consisting of Lactobacillus johnsonii La1 (CNCMI-1225), Bifidobacterium longum (CNCM I-2170), Bifidobacterium lactisBb12 (German Culture Collection: DSM20215), (Lactobacillus paracasei(CNCM I-2116, CNCM I-1292)), Lactobacillus rhamnosus GG, Streptococcusfaecium SF 68, and mixtures thereof.

In one embodiment of the present invention, the nutritional compositionand/or the medicament further comprises additional non-viable probioticbacteria and/or probiotic-derived material. Probiotic derived materialcan be any material that is derived from the probiotics themselves, suchas, e.g., a cellular fraction or a compound or a group of compoundsisolated from probiotics; or it can be material that was produced withthe help of probiotics, such as culture medium or a part thereof, whereprobiotics were cultivated or a product that was modified with the helpof probiotics; or a mixture thereof.

Preferably the nutritional composition and/or the medicament prepared bythe use of the present invention further comprises fermentationsubstrate of the probiotics. It was found that this supports theviability of the probiotics, e.g., during storage times.

In one embodiment of the present invention the composition and/or themedicament prepared by the use of the present invention furthercomprises one or more prebiotics. Prebiotics are for the purpose of thepresent invention non-digestible food ingredients that beneficiallyaffect the host by selectively stimulating the growth and/or activity ofone or more bacteria in the colon.

Prebiotics have the advantage that they support the growth of beneficialbacteria in the colon of the patient. They furthermore support theviability of living probiotics present in the composition and/or themedicament prepared by the use of the present invention, both duringstorage times and after consumption by the patient.

A patient can be a human or an animal. Preferred animals are pet animalsand livestock.

In one embodiment of the present invention, the nutritional compositionand/or the medicament prepared by the use of the present inventioncomprises probiotics in an amount of about 10⁵-10¹¹ cfu/ml, preferablyabout 10⁶-10 ⁹ cfu/ml, most preferred about 10⁷-10 ⁸ cfu/ml. It is tounderstood, however, that the optimal amount of probiotics is to bedetermined by medical personal, since this depends on numerous factors,such as, e.g., the kind, age, sex, condition, body weight of the patientas well as on the nature of the product. Usually, medicaments willcontain higher amounts of probiotics than nutritional compositions. Ingeneral any amount of probiotics will produce a beneficial effect.

The composition of the present invention comprises in one embodimentfurther a carbohydrate source, a lipid source and/or a protein source.

The composition of the present invention is to be understood as thenutritional composition and/or the medicament prepared by the use of thepresent invention.

The nutritional composition and/or the medicament may include a lipidsource.

Preferably the lipid source provides about 18% to about 50% of theenergy of the nutritional composition, more preferably about 25% toabout 35% of total energy of a nutritional composition, most preferablyabout 30% of total energy of the composition.

The lipid source may include medium chain triglycerides (MCT), forexample up to a level of 20% of the total lipid by weight. Such mediumchain triglycerides are easily absorbed and metabolized in the acutelyill, catabolic patient. In a preferred embodiment, the medium chaintriglyceride source is fractionated coconut oil.

The lipid profile may also comprise a mixture of long chaintriglycerides. Suitable sources of long chain triglycerides are canolaoil, corn oil, soy lecithin and residual milk fat. The lipid source mayalso contain polyunsaturated fatty acids. Preferably the lipid sourcecontains about 15% to about 30% by weight of polyunsaturated fattyacids; for example about 20% by weight of polyunsaturated fatty acids.

The lipid profiles containing long chain triglycerides are designed tohave a polyunsaturated fatty acid omega-6 (n-6) to omega-3 (n-3) ratioof approximately 1:1 to 10:1. Preferably, the n-6 to n-3 fatty acidratio is about 5:1 to about 9:1; for example about 7:1. The proposedratio of n-6:n-3 is designed to reduce the immune suppression associatedwith high omega-3 fatty acid concentration and to provide adequateessential fatty acids. In an embodiment, the composition includes anomega-6 to omega-3 ratio of 7.7:1.

The lipid source is preferably rich in monounsaturated fatty acids. Inparticular, the lipid source contains at least about 40% by weight ofmonounsaturated fatty acids. Preferably, the lipid source contains about45% to about 65% by weight of monounsaturated fatty acids; for exampleabout 55% by weight.

The lipid source has preferably a saturated fatty acid content of lessthan about 35% by weight; including medium chain triglycerides. Morepreferably, the lipid source contains less than about 30% by weight ofsaturated fatty acids.

Suitable lipid sources include high oleic sunflower oil, high oleicsafflower oil, sunflower oil, safflower, rapeseed oil, soy oil, oliveoil, canola oil, corn oil, peanut oil, rice bran oil, butter fat,hazelnut oil and structured lipids. Fractionated coconut oils are asuitable source of medium chain triglycerides.

The lipid source may also contain vitamin E, preferably at least about30 mg of vitamin E per 100 g of lipid source.

The nutritional composition and/or the medicament may include acarbohydrate source.

Preferably the carbohydrate source comprises maltodextrin, corn syrup,corn starch, modified starch, or sucrose, or fructose, or mixturesthereof. The carbohydrate source preferably provides at least about 15%,preferably about 20%-40%, of the total calories of the composition, orabout 40% to about 65% of the energy of the nutritional supplement;especially about 50% to about 60% of the energy of the nutritionalcomposition. For example, the carbohydrate source may provide about 54%of the energy of the supplement.

If desired, the nutritional composition and/or the medicament may befree from lactose.

E.g., to avoid occurrence of diarrhoea the composition may also containa dietary fibre, preferably in an amount of at least 8 g/l, mostpreferably in an amount of at least 14 g/l.

Hence, preferably the nutritional composition and/or the medicamentfurther includes a source of a soluble, prebiotic fibre. A prebioticfibre is a fibre which beneficially affects the host by selectivelystimulating growth and/or activity of bacteria in the colon which havethe potential to improve host health. Suitable soluble, prebiotic fibresinclude fructooligosaccharides (FOS) and inulin. Suitable inulinextracts may be obtained from Orafti SA of Tirlemont 3300, Belgium underthe trade mark “Raftiline”. Similarly, suitable fructooligosaccharidesmay be obtained from Orafti SA of Tirlemont 3300, Belgium under thetrade mark “Raftilose”.

Preferably, both FOS and inulin are provided in a ratio of about60:about 40 to about 80:about 20, most preferably about 70:about 30.Other possible fibres include gums such as guar gum, xanthan gum,xylo-oligosaccharides, gum arabic, pectin, acacia gum, resistant starch,dextrans or mixtures of these. The fibre selected should preferably notinduce satiety.

The soluble, prebiotic fibres are reported to promote the growth ofbifidobacteria in the gastrointestinal tract and, in certaincircumstances prevent or decrease the growth of pathogens such asClostridiae. Further, promoting the growth of bifidobacteria is reportedto have various other beneficial effects. Also, during fermentation ofthe fibres in the colon, short chain fatty acids are produced. Thesefatty acids are a fuel for intestinal cells.

The soluble, prebiotic fibres are preferably present in an amountsufficient to provide about 4 to about 9 g of soluble, fermentable fibreto the patient per day. Therefore the prebiotic fibres may be present inan amount of about 6 g to about 12 g per 1000 kcal. Alternativeembodiments comprise blends of prebiotic fibres in an amount of 9 g orless, for example 4 g of blend.

If desired, the nutritional supplement may also contain a source ofinsoluble dietary fibre. Suitable sources of insoluble dietary fibresare hull fibres from legumes and grains; for example pea hull fibre, oathull fibre, barley hull fibre, and soy hull fibre.

Similarly, the osmolality of the nutritional composition can be adjustedto the intended purpose, e.g, to avoid diarrhoea, in particular to beless than 500 mOsm, more preferred to be less than 300 mOsm, e.g., to anosmolality of about 100 to 250 mOsm. Flavoured products usually have ahigher osmolality than unflavoured products.

The nutritional composition and/or the medicament may include a proteinsource.

The protein source may include at least about 50% by weight of wheyprotein that preferably has been at least partially hydrolyzed. The wheyprotein used to produce the hydrolysate may be a commercially availablewhey protein source; either based upon sweet whey or acid whey or acombination thereof. Preferably the whey protein is a whey proteinsource containing more than 80% by weight of whey protein. A suitablewhey protein concentrate is LACPRODAN 9087 and suitable whey proteinisolate sources include ALACEN 895 (New Zealand Milk Products Inc),BiPRO (Le Sueur Isolates of Le Sueur, Minn.), PROVON-190 (AvonmoreIngredients Inc of Monroe Wis.) and LACPRODAN 9212 (Royal Proteins, Incof Rosemont Ill.).

The protein source may, if desired, include amounts of other suitabletypes of protein. For example, the protein source may further includeminor amounts of casein protein, soy protein, rice protein, pea protein,carob protein, oat protein, milk protein, caseino-glyco-macropeptide ormixtures of these proteins. Further, if desired, the protein source mayfurther include minor amounts of free amino acids. The other suitabletypes of protein preferably comprise less than about 50-% by weight ofthe protein source; more preferably less than about 30% by weight.

Depending on the condition the patient is in, the protein source ispreferably selected so that the resulting food composition is easy todigest.

A high protein concentration may be used to provide sufficient proteinto replete lean body mass in patients with elevated protein losses.Elevated protein requirements have been identified in patientpopulations such as pressure ulcer, serious wounds, trauma, Crohn'sdisease with protein-losing enteropathy, chronic diarrhea, and HIV/AIDSmalabsorption and diarrhea. Inherent to the metabolic requirements ofthese conditions is an increased loss of nitrogen, increased requirementfor protein or both.

The composition of the present invention may be designed to be apeptide-based diet. In choosing the protein source, the presentinvention maximizes tolerance and absorption with the use of ahydrolyzed protein. In a preferred embodiment, the protein source isenzymatically hydrolyzed whey protein. This type of protein sourcereduces the incidence of gastric reflux because gastric emptying isfaster than with diets containing casein or whole whey. Also, hydrolyzedwhey protein serves as a rich source of the amino acid cysteine, whichis a limiting amino acid for the formation of glutathione.

The protein source preferably provides about 8% to about 25% of theenergy of the nutritional supplement. According to one embodiment of thepresent invention the protein source provides at least about 8%,preferably about 15%-25%, of the total calories of the composition. Forexample, the protein source may provide about 15% to about 18% of theenergy of the composition in an embodiment suitable for an adult orabout 8% to about 14% of the energy of the supplement in an embodimentsuitable for pediatric use.

In a particular preferred embodiment of the present invention theprotein source provides at least about 8%, preferably about 15%-25%, ofthe total calories of the composition, the lipid source provides atleast about 18%, preferably about 30%-50%, of the total calories of thecomposition and preferably has an omega 6 to omega 3 fatty acid ratio ofapproximately 2:1 to about 10:1, and the carbohydrate source provides atleast about 15%, preferably about 20%-40%, of the total calories of thecomposition.

In one embodiment of the present invention the nutritional compositionor the medicament further comprises micronutrients, preferably selectedfrom the group consisting of comprising at least vitamin E and vitaminC.

Even more preferred the nutritional composition and/or the medicamentcomprises a complete vitamin and mineral profile. For example,sufficient vitamins and minerals may be provided to supply about 50% toabout 500% of the recommended daily allowance of the vitamins andminerals per 1000 calories of the nutritional supplement. Thenutritional composition and/or the medicament preferably is rich invitamin E. For example, the nutritional composition and/or themedicament may contain between 80 International Units and 120International Units of Vitamin E per 1000 kcal. More preferably, thenutritional supplement contains about 30 International Units of VitaminE per 250 ml serving of the supplement.

Furthermore the nutritional composition and/or the medicament is alsorich in Vitamin C providing between about 150 and about 250 mg per 1000kcal or preferably about 60 mg per serving. Vitamin C is believed toaccelerate the healing and granulation in patients with severe healingrequirements. Vitamin C will support increased requirements/losses aftersurgery.

The nutritional composition and/or the medicament also preferablycontains 200 g of folic acid and 3 g of Vitamin B-12 per dosage form.Alternative embodiments of the nutritional composition and/or themedicament for pediatric use have a modified vitamin and mineral profilespecifically tailored to the special needs of this age group.

Pursuant to the present invention, the composition may also include ahigh level of zinc. Preferably, at least approximately 150% of the USRDAof zinc is provided in the composition per 1000 Kcal. In an embodiment,19 to 29 mg per 1000 calories of zinc are provided. In a preferredembodiment, 24 mg per 1000 calories of zinc is provided. The increasedzinc compensates for zinc losses and provides increased zinc for tissuerepair in a patient having increased healing requirements.

Pursuant to the present invention, the composition may also includeincreased amounts of selenium. Selenium deficiencies may develop inpatients having elevated healing requirements. Pursuant to the presentinvention, at least approximately 40 to 60 μg of selenium are providedin 1000 calories of formula. In a preferred embodiment, approximately 50μg of selenium per 1000 calories is provided.

The composition of the present invention may also include a source ofbeta-carotene. Beta-carotene can be added to the composition tonormalize beta-carotene serum plasma levels and avoid beta-carotenedeficiency in long term tube-fed patients. The composition preferablyincludes approximately 1.6 to 2.4 mg per 1000 calories. This amountprevents deficiencies and provides for possible increased requirementsin the healing patient. Moreover, the beta-carotene levels allow plasmaconcentrations to be increased to near normal optimal levels of 500 mcgper liter.

The composition of present invention may also provide increased amountsof L-carnitine and taurine to support the increased requirements of theacutely ill, catabolic patient. Both taurine and L-carnitine arepreferably present in amounts of approximately 80 to 120 mg per 1000calories. In preferred embodiments, both taurine and L-carnitine arepresent in an amount of approximately 100 mg per 1000 calories.

Still further, the composition of the present invention includesdecreased amounts of magnesium. Magnesium has been associated withdiarrhea. In an embodiment, magnesium is present in an amount ofapproximately 237 mg to 355 mg per 1000 calories. In a preferredembodiment, magnesium is present in an amount of approximately 300 mgper 1000 calories.

The nutritional composition of the present invention preferably has anenergy content of about 800 kcal/l to about 2000 kcal/l; for example anenergy content of about 1000 kcal/l or about 1500 kcal/l. Preferably,the caloric density of the composition is 1.0 kcal/ml.

The nutritional composition and/or the medicament may be in the form ofa soluble powder, a liquid concentrate, a pudding, a bar/snack or aready-to-use formulation suitable for oral consumption or enteraladministration. Ready to drink formulations are particularly preferred.Various flavours, sweeteners, and other additives may also be present.Artificial sweeteners such as acetosulfame and L-aspartyl basedsweeteners may be used; for example acesulfame-K or aspartame or amixture thereof.

The composition of the present invention is preferably a ready-to-useenteral formulation. The composition can be used as a supplement or fortotal enteral nutritional support. The composition can be tube-fed to apatient, or fed by having the patient drink same.

The amount of the nutritional composition and/or the medicament requiredto be fed to a patient will vary depending upon factors such as thepatient's condition, the patient's body weight, the age of the patient,and other sources of nutrition. However the required amount may bereadily set by a medical practitioner. The nutritional supplement may betaken in multiple doses, for example 2 to 5 times, to make up therequired daily amount or may be taken in a single dose.

Those skilled in the art will understand that they can combine anyfeatures described in this specification without departing from thescope of the invention as disclosed.

Further embodiments and advantages of the present invention will beevident from the following Examples and Figures.

FIG. 1 shows the level of colonization of the large bowel byLactobacillus johnsonii La1 expressed in Ia log₁₀ scale. Displayed aremean values and the corresponding standard derivations for group A(placebo), group B (10⁷ cfu) and group C (10⁹ cfu).

EXAMPLE 1

The intestinal microbiota comprises an extremely high number of microbesof different cell lineage that can communicate with each other and thehost. Overall the microbiota is a real organ that is implicated in amultitude of functions that contributes to the health of the host. Itrecovers energy from complex carbohydrates that escape the digestion ofhost enzymes in the small bowel, it plays an important role in theprevention of colonization by pathogenic bacteria and it contributes topreserve the mucosal barrier and to modulate the inflammatory/immunereactivity of the mucosa. Interestingly after subtotal and totalcolectomy the metabolic and protective activities of the microbiota aredecreased and therefore post surgical complications can be enhanced dueto the transient impaired microbiota function. It is known that patientsundergoing colorectal surgery have a high risk of postsurgicalinfection. The capacity to restitute a colonic microbiota as soon aspossible with a predominance of the probiotic protective strains canplay a protective role during this critical moment. The aim of thisstudy is to demonstrate that it is possible to colonize the colon of apatient in the peri-surgical period with probiotic strains byadministration as a dietary supplement before and after the operation,despite the special condition the patient to be treated is in. Usuallypatients are under a significant amount of stress, are under heavyantibiotic treatment, might suffer from an impaired immune system and/orare at a significant danger of being colonized by pathogenic andantibiotic resistant bacteria that appear more and more often inrepeatedly sterilized environments such as hospitals.

Patients and Methods.

30 subjects suffering from colonic adenocarcinoma were enrolled in adouble-blinded study and randomly distributed into three groups:

Group 1: Probiotics at high dose (10⁹ cfu).Group 2: Probiotics at low dose (10⁷ cfu).Group 3: placebo.

Treatment.

The treatments were composed of Lactobacillus johnsonii La1 andBifidobacterium BB536 (both bacterial strains were present at the samecfu level in the two products) blended with maltodextrin. The placebowas maltodextrin only.

The treatments started 3 days before surgery, were stopped the day ofthe surgery and were resumed after surgery until 12 days after surgery.

Main Parameter.

The primary outcome of the study was the luminal or mucosal colonizationassessed at the moment of surgery.

Results.

Group codes were A (placebo), B (probiotics at 10⁷) and C (probiotics at10⁹). The colonization at D0 (day of surgery) in colonic content ormucosal biopsy with Lactobacillus johnsonii La1 was demonstrated in 3out of 11 patients in group B and in 4 out of 9 patients in group C.

TABLE 1 Presence of bacteria in the colonic content or mucosal biopsy NoYes La1 A 10 0 B 8 3 C 5 4

Conclusions.

These results demonstrate that a typical probiotic, Lactobacillusjohnsonii La1, is able to colonize the distal colon in patients that areundergoing colectomy due to colo-rectal adenocarcinoma. Patientssuffering from these conditions and undergoing the surgical treatmentare under stress and suffer from local major ecological modifications inthe colon. Indeed colonic microbiota modifications occur as a result ofdramatic alterations in the redox status of the colonic environment,antibiotic treatment and the intestinal lavage that gets rid of most ofthe lumenal biomass. The possibility to preserve a stable population ofprobiotic bacteria will create the basic condition for microbiotareconstitution. This in turn results in a better post-operation clinicalcondition of the patient by preventing infectious complications and byrestoring the physiology of the colon that depends on a metabolicallyactive microflora.

EXAMPLE 2

A typical nutritional formulation prepared by the present invention ispresented below:

The nutritional formulation is in this case a food preparationconsisting of a mixture proteins, carbohydrates, fats, vitamins andminerals in amounts intended to meet 33% of the daily nutrientrequirements of an adult person when 500 ml are consumed.

16% of the energy are provided by the protein fraction, 34% by the fatsand 50% by the carbohydrates.

The protein source is 50% whey protein and 50% casein and thereconstituted powder contains 4 g of proteins per 100 ml (100 Kcal).

The lipid fraction is composed of rapeseed oil, medium chaintriglycerides (MCT) and corn oil. MCT represent 25% of the lipids. Thefatty acid profile is composed of 20% saturated fatty acids (FA), 40%monounsaturated fatty acids and 40% of polyunsaturated fatty acids. Then-6/n-3 fatty acid ratio is 4:1.

The carbohydrate content is 12.6 g per 100 ml of the reconstitutedpowder and is provided by maltodextrins. The product is lactose free.

The composition contains fibre provided by oligosaccharides (inulin) ina concentration of 1.5 g per 100 ml.

The powder contains spray dried Lactobacillus johnsonii La1 in aconcentration of 10⁸ cfu per g of powder.

This standard reconstitution of the resulting product is 22 g ofpowder+84 ml of water for a serving of 100 ml.

1. The use of a probiotic or of a mixture of probiotics in themanufacture of a nutritional composition or a medicament to act thecolon in a pre- or post surgical environment.
 2. The use according toclaim 1 wherein the probiotics act by a reaching the colon alive, inparticular by colonizing the colon.
 3. The use according to claim 1wherein the nutritional composition or the medicament is for theprevention and management of non-infectious diarrhoea.
 4. The useaccording to claim 1 wherein the nutritional composition or themedicament is for the prevention of postsurgical abdominal-pelvicinfections due to pelvic fluid collection secondary to leakiness in theanastomosis or bacterial translocation.
 5. The use according to claim 1wherein the nutritional composition or the medicament is for theprevention or alleviation of gastrointestinal symptoms secondary toglobal changes in the intestinal microbial ecology and the microbiotametabolic activity, preferably infectious or toxigenic diarrhoea.
 6. Theuse according to claim 1 wherein the nutritional composition or themedicament is for the prevention or treatment of gastrointestinalinfections, preferably nosocomial gastrointestinal infections.
 7. Theuse according to claim 1 wherein the nutritional composition or themedicament is for modulating the inflammatory response, in particularduring the healing process.
 8. The use according to claim 1 wherein thenutritional composition or the medicament is for modulating the immunesystem and/or for stimulating the production of mucosal secretoryantibodies.
 9. The use according to any of claims 1 to 8, wherein theselected probiotic is selected from the group consisting ofBifidobacterium, Lactobacillus, Streptococcus and Saccharomyces ormixtures thereof.
 10. The use according to any of claims 1 to 9, whereinthe selected probiotic is selected from the group consisting ofBifidobacterium longum, Bifidobacterium lactis, Lactobacillusacidophilus, Lactobacillus rhamnosus, Lactobacillus johnsonii,Lactobacillus plantarum, Lactobacillus salivarius, Streptococcusfaecium, Saccharomyces boulardii and Lactobacillus reuteri or mixturesthereof.
 11. The use according to any of claims 1 to 10, wherein theselected probiotic is selected from the group consisting ofLactobacillus johnsonii La1 (CNCM I-1225), Bifidobacterium longum (CNCMI-2170), Bifidobacterium lactis Bb12 (German Culture Collection:DSM20215), (Lactobacillus paracasei (CNCM I-2116, CNCM I-1292)),Lactobacillus rhamnosus GG, Streptococcus faecium SF 68, and mixturesthereof.
 12. The use according to any one of the preceding claims,wherein the nutritional composition or the medicament further comprisesnon-viable probiotic bacteria and/or probiotic-derived material.
 13. Theuse according to any one of the preceding claims, wherein thenutritional composition or the medicament further comprises thefermentation substrate of the probiotics.
 14. The use according to anyone of the preceding claims, wherein the nutritional composition or themedicament further comprises prebiotics.
 15. The use according to anyone of the preceding claims, wherein the probiotic is present in anamount of about 10⁵-10¹¹ cfu/ml, preferably about 10⁶-10⁹ cfu/ml, mostpreferred about 10⁷-10⁸ cfu/ml.
 16. The use according to any one of thepreceding claims, wherein the nutritional composition further comprisesa carbohydrate source, a lipid source and a protein source.
 17. The useaccording to claim 16, wherein the protein source provides at leastabout 8%, preferably about 15%-25%, of the total calories of thecomposition, the lipid source provides at least about 18%, preferablyabout 30%-50%, of the total calories of the composition and preferablyhas an omega 6 to 3 fatty acid ratio of approximately 2:1 to about 10:1,the carbohydrate source provides at least about 15%, preferably about20%-40%, of the total calories of the composition.
 18. The use accordingto any one of the preceding claims, wherein the nutritional compositionor the medicament further comprises micronutrients, preferably selectedfrom the group consisting of comprising at least vitamin E and vitaminC.